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Introduction Exercise plays an important role in cancer rehabilitation, but a precise prescription of exercise intensity is required to maximize the benefits of this intervention. It is unknown whether different methods of prescribing aerobic exercise intensity achieve the same intensity. Breast cancer treatments may alter exercise response and thereby may affect the accuracy of these methods.

Purpose The purpose of this study was to compare the accuracy and achieved intensity of four common methods of prescribing exercise intensity within and between breast cancer patients recently finished chemotherapy (n = 10), survivors finished treatment (n = 10), and healthy controls (n = 10).

Results The accuracy of the methods was not equivalent across groups (P = 0.04). HRR and METW did not differ across groups and were most accurate in patients. HRR, METW, and DIRECT HR were all more accurate than RPE in survivors (P ≤ 0.01). RPE was the least accurate in all groups. The accuracy of DIRECT HR was much lower in patients than that in survivors and controls (P ≤ 0.01).

Conclusions The four methods of exercise intensity prescription varied in accuracy in prescribing 60% V˙O2R and did not achieve equivalent exercise intensities within breast cancer patients, survivors, and healthy controls. HRR and METW were the most accurate methods for exercise intensity prescription in breast cancer patients and survivors.

1School of Kinesiology, University of British Columbia, Vancouver, BC, CANADA; 2Department of Physical Therapy, University of British Columbia, Vancouver, BC, CANADA; and 3Division of Sports Medicine, Department of Family Practice, University of British Columbia, Vancouver, BC, CANADA

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.acsm-msse.org).

Exercise plays a significant role in improving physical function and quality of life in breast cancer survivors (22). An exercise prescription includes the parameters of frequency, intensity, time, and type of activity (i.e., aerobic or resistance) (27). As with the other aspects of patient management, the prescription of this intervention requires precision in its application to maximize its health benefits and to reduce risk of adverse events. It has been demonstrated in noncancer populations that aerobic exercise intensity has a positive relationship with health and a negative relationship with all-cause mortality (2,25,26). Thus, exercise intensity prescription should be considered a critical parameter of exercise for breast cancer populations and a topic of high priority in oncological patient rehabilitation.

There are several different methods of prescribing exercise intensity for aerobic exercise. Each method uses physiological relationships, assumptions, and/or metabolic constants to determine a target for exercise in the form of a specific heart rate, exercise workload, or RPE. The underlying principle in using these methods is that when the prescribed target is achieved, the intensity of the exercise, as measured by the volume of oxygen being consumed in the body (V˙O2), is equivalent to the intensity level prescribed. In the breast cancer population, the scientific basis of exercise intensity prescription methods is complicated by the side effects of adjuvant treatment that affect oxygen delivery and thereby the physiological relationships and variables involved in exercise intensity prescription, such as anemia, and subclinical effects of cardiotoxicity and pulmonary toxicity (17).

The level of accuracy or the extent to which exercise intensity prescription methods achieve the desired intensity in breast cancer populations is unknown. Accuracy should be an important consideration in method choice, as it will affect the efficacy and thereby the outcome measures of the exercise program implemented, whether in research or clinical practice. Accuracy also has potential safety implications, as the effects of high intensity exercise on the immune system in this population are not known (21). In addition, there are no studies available in any population comparing all exercise intensity prescription methods simultaneously, and therefore it cannot be assumed that the intensity achieved by each method is equivalent to each other (27). The development of cancer-specific exercise guidelines is a current high-priority objective. A few accurate methods of aerobic exercise intensity prescription that will achieve similar intensities relative to one another are fundamental to increasing compliance with intensity recommendations, both clinically and in research.

A pragmatic, cross-sectional study was performed with the primary objective of comparing the accuracy and achieved intensity of four common exercise intensity prescription methods in breast cancer patients and survivors. A secondary objective was to determine whether breast cancer treatment status (i.e., during treatment, after treatment, or no adjuvant treatment) affected the accuracy of the exercise intensity prescription methods.

PATIENTS AND METHODS

Participants

To capture different phases across the breast cancer treatment trajectory and to compare women in these phases to women without cancer, three distinct participant groups were recruited: 1) the patient group (n = 10) were women who had received their last adjuvant chemotherapy treatment for stages I–IIIA breast cancer 2–4 wk before testing; 2) the survivor group (n = 10) were women who had completed adjuvant chemotherapy and radiation treatment for stages I–IIIA breast cancer 1–3 yr before testing; and 3) the control group (n = 10) were women with no history of cancer. Participants were 40–65 yr old; had not experienced a menstrual cycle for at least 3 months to standardize the effect of hormone status on exercise response (30); self-reported at least 30 min of moderate intensity exercise, three times per week in the last month to ensure their safe completion of the study protocol; and had the ability to understand and provide written informed consent in English. Exclusion criteria included the diagnosis of any other major illness or disease, the use of medications that alter the heart rate response (i.e., β-blockers), and other contraindications to exercise (e.g., uncontrolled hypertension and psychiatric illness).

Patient and survivor group participants were recruited from past exercise intervention studies in our laboratory so that they had experience with exercise testing, treadmill use, and the Borg RPE scale to minimize confounding effects such as anxiety and inexperience. Control group participants were recruited from community centers and had no previous experience with exercise testing. On completion of the study, participants were offered an aerobic exercise prescription. The study received ethical approval from the Clinical Research Ethics Board at The University of British Columbia, and written informed consent was obtained from all participants.

Measurements

The study protocol involved two visits for each participant. Participants were asked to abstain from strenuous exercise for 24 h, alcohol and nonprescription drugs for 12 h, caffeine for 4 h, and food for 1 h before both visits.

At visit 1, participants completed a Physical Activity Readiness Questionnaire (Canadian Society of Exercise Physiology, Ottawa, ON) and a maximal incremental treadmill (Precor USA, Helsinki, Finland) exercise test to volitional exhaustion. The exercise test protocol consisted of a constant walking speed, determined during the 5-min warm-up preceding the test, and a 1% grade to start, followed by an increase of 2% at the end of every 2-min stage. The speed was chosen jointly by the subject and the investigator based on the elicitation of natural walking biomechanics (as opposed to a walk–run transition) and a feeling of a comfortable, but strong pace, intended to produce a test length of 8–15 min. The authors have used this protocol extensively with breast cancer populations (5,7). Expired gases and heart rate were collected, analyzed, and averaged for 15-s periods by a Parvo Medics’ TrueOne 2400 metabolic cart (Parvo Medics, Sandy, UT). At the end of every stage, participants indicated their RPE on the Borg category scale and were given standardized instructions on the use of the RPE scale before the test (see text, Supplemental Digital Content 1, http://links.lww.com/MSS/A215, standardized RPE instructions given to study participants). Participants were not allowed to hold on to hand rails and were verbally encouraged throughout the test. The cart was calibrated before and verified immediately after each test.

The accuracy and the achieved intensity of the four common exercise intensity prescription methods for aerobic exercise were measured at visit 2, which was within 2–14 d of visit 1. The four exercise intensity prescription methods compared were 1) the American College of Sports Medicine’s metabolic equation for treadmill walking (METW), 2) the direct measured relationship between heart rate and V˙O2 (DIRECT HR), 3) the heart rate reserve (HRR) or Karvonen method, and 4) the RPE method (27). The procedures for applying each of these methods are outlined in Table 1. Each method was used to prescribe an exercise intensity of 60% of oxygen consumption reserve (V˙O2R) during a 10-min bout of walking exercise on the treadmill. V˙O2R is the preferred expression of exercise intensity for exercise prescription (13) and is equivalent to the difference between peak oxygen consumption (V˙O2peak) and resting oxygen consumption (V˙O2rest). The target V˙O2 was calculated by multiplying the desired exercise intensity (i.e., 60% = 0.6) by each participant’s measured V˙O2R and then by adding the measured V˙O2rest.

The exercise intensity prescription methods were applied in a randomized order (Research Randomizer, www.randomizer.org) for each participant. Expired gases were measured during each bout using the metabolic cart to give an accurate quantification of the exercise intensity (% V˙O2R) achieved during each exercise bout (8). A warm-up and ramp to achieving the target (a heart rate, exercise workload, or RPE) for each exercise bout was performed within the first 5 min of each bout. The target was then held constant for the last 5 min of the bout to achieve steady-state V˙O2. A minimum 10-min rest took place in between each exercise bout, where subjects were encouraged to sit in front of a fan and hydrate in attempts to prevent cardiovascular drift after the first bout (15). The next exercise bout was not started until the subject achieved a seated heart rate within 5–10 beats of their resting heart rate.

All methods were implemented in a way that closely approximates the way they would be used in practice in a research or clinical setting, with a few exceptions for the equipment. For example, the investigators operated the treadmill speed and grade adjustments, as the pneumotach and tubing prevents full view and operation of treadmill buttons by participant. The details regarding the application of these exercise intensity prescription methods are described in Table 1 (and see text, Supplemental Digital Content 2, http://links.lww.com/MSS/A216, details of how each exercise intensity prescription method was implemented during the study). The variables required to apply each method were acquired during the exercise test on visit 1, except for V˙O2rest and resting heart rate (HRrest), which were collected at the beginning of visit 2. HRrest was recorded using a Polar A3 heart rate monitor (Polar Electro Canada Inc., Lachine, QC) as the lowest single heart rate value achieved during 10 min of quiet, seated rest. V˙O2rest was obtained immediately after by measuring expired gases for another period of 10 min of quiet, seated rest, or until steady V˙O2 measurements were seen for four consecutive 30-s periods.

The achieved intensity of the exercise intensity prescription methods was defined as an average of the % V˙O2R measured by the metabolic cart during the last 5 min of each exercise bout. The accuracy of the exercise intensity prescription methods was defined as the absolute value of the difference between the prescribed intensity of 60% V˙O2R and the achieved intensity. Accuracy is reported in percentage points, the arithmetic difference between two percentages, and lower values indicate more accuracy and less variation from the prescribed intensity.

Statistical analysis

Descriptive statistics are presented as mean ± SD. Participant characteristics were compared between groups by ANOVA. The accuracy and the achieved intensity of the four exercise intensity prescription methods within each group were analyzed with a one-way ANOVA for the three groups independently. When the equality of variance assumption was violated, the Welch statistic was used and is reported (12). Post hoc comparisons were performed using the Tukey HSD test or the Games–Howell test for nonhomogeneous variances (12). Independence between the exercise intensity prescription methods was assumed for each participant. An outlier was defined as a value larger than 1.5 times the interquartile range and was removed for inferential analysis. The effect of breast cancer adjuvant treatment status on the accuracy of the exercise intensity prescription methods was analyzed with a 3 group × 4 method ANOVA, followed by post hoc hand-calculated orthogonal contrasts (see table, Supplemental Digital Content 3, http://links.lww.com/MSS/A217, hand statistical calculations performed for the orthogonal contrasts used to investigate the exercise intensity prescription method accuracy by breast cancer treatment status interaction) planned from the mean accuracy differences for each method. All other data were analyzed using PASW Statistics 18. The alpha level was set at P = 0.05 for all analyses, and the Bonferroni correction was made when necessary. Effect size was calculated with a 5% V˙O2R or a 5 percentage point difference between methods for a single group. Eight subjects per group were required to achieve a power of 0.8.

RESULTS

Participant characteristics are reported in Table 2. Participants were similar across groups, with two exceptions. The patient group was younger (mean age = 47.7 yr) than the control group (mean age = 54.3 yr) (P < 0.01). The survivor group was taller than the control group (P = 0.01) but did not differ in body mass index (P = 0.22). Relative V˙O2peak and V˙O2rest values were lowest in the patient group and highest in the control group but not significant (P = 0.29 and 0.11, respectively). In addition, HRrest, HRpeak, and HRR approached significance but were not different (P = 0.15, 0.12, and 0.10, respectively). The successful attainment of V˙O2peak (classified as achievement of three out of four criteria of volitional exhaustion, occurrence of a 15-s plateau in V˙O2 concurrent with increased workload, an RER greater than 1.1, and peak heart rate within 5 bpm of the age-predicted maximal heart rate [HRmax = 206.9 − (0.67 × age)] [14]) was similar among groups with seven, nine, and nine participants from the patient, survivor, and control groups, respectively (data not shown). At the time of testing, the patient group had completed adjuvant chemotherapy with a mean of 3.5 wk and the survivor group with a mean of 87.5 wk (1.7 yr) prior.

Accuracy and achieved intensity

The average number of beats per minute above resting heart rate before beginning successive exercise bouts ranged from 3 to 5 and did not statistically differ across groups or methods (data not shown), indicating some consistency in conditions for evaluating each method. The accuracy and achieved intensity of the exercise intensity prescription methods within each group are reported in Table 3. There were significant differences in accuracy among the four exercise intensity prescription methods in the patient (P = 0.04), survivor (P < 0.01), and control (P = 0.02) groups. In addition, there were significant differences in achieved intensity in the patient (P < 0.01), survivor (P < 0.01), and control (P < 0.01) groups. In the patient group, the RPE method had lower accuracy (P = 0.05) and achieved intensity (P = 0.02) than the HRR method and was the least accurate method. The HRR method was the most accurate in this group. Although the accuracy of the DIRECT HR method was just as low as the RPE method (P = 1.00), it had a higher achieved intensity (P = 0.01). In the survivor group, the accuracy of the RPE method was lower than all three other methods (METW, P < 0.01; DIRECT HR, P < 0.01; HRR, P = 0.01). The mean achieved intensity of the RPE method was also lower than the three other methods (all at P < 0.01). METW, DIRECT HR, and HRR were all similar in accuracy and achieved intensity. In the control group, the accuracy of the METW method was higher than both the RPE method (P < 0.01) and the HRR method (P < 0.01). The achieved intensity of the METW method was lower than the HRR method (P = 0.02).

Breast cancer treatment status had a medium to large effect (partial η2 = 0.12) on the accuracy of the exercise intensity prescription methods (P = 0.04). Four post hoc contrasts, one for each exercise intensity prescription method, were required to further investigate the interaction, as such the pairwise alpha was adjusted to P = 0.01. For both the METW and the HRR methods, there was no significant difference in accuracy between the patient and control groups (both P > 0.01). For the DIRECT HR method, the survivor and the control groups had the same mean accuracy and so were combined and compared with the patient group, and this contrast was significant (P ≤ 0.01). For the RPE method, the patient and control groups were combined and compared with the survivor group, and this contrast was significant (P ≤ 0.01). Therefore, adjuvant breast cancer treatment affected the accuracy of the DIRECT HR and RPE methods only.

DISCUSSION

This study was the first to simultaneously compare four common exercise intensity prescription methods in any population. There were statistically significant differences in the accuracy and achieved intensity of the four exercise intensity prescription methods within the patient, the survivor, and the control groups. In addition, the accuracy of some of the exercise intensity prescription methods was not the same between the three groups. The results of the study can be used for the prescription of exercise in clinical practice, involving breast cancer patients during or immediately after chemotherapy and survivors after completion of initial treatment, and for future research involving exercise interventions for these populations. The results can also be used to compare the intensities prescribed in previous research and in the development of safe and effective exercise intensity guidelines for breast cancer.

The METW method was the most accurate in the survivor and control groups and was only one percentage point lower than the HRR method in the patient group. The application of this exercise intensity prescription method requires measured V˙O2rest and V˙O2peak values, which will change due to deconditioning, exercise capacity improvements in an aerobic exercise program or with changes in metabolic rate that are possible throughout chemotherapy treatment (9,16,27). Therefore, to maximize the accuracy of this method, frequent maximal cardiopulmonary testing and measurement of V˙O2rest would be required. This requirement for frequent testing to gain and maintain accuracy may make this method of exercise intensity prescription inappropriate for certain settings. Maximal exercise testing has been reported to be relatively safe in the cancer population (18), but it may not be feasible to do in a clinical setting or repetitively during chemotherapy treatment. However, there are other situations where the accuracy of this method would make it an ideal choice. For example, maximal accuracy in exercise intensity prescription would be required in research studies where the primary outcome is contingent on exercise at a specific intensity or the effect of different exercise intensities is being compared. A possible explanation for the lack of difference among the groups for this method is that V˙O2rest was measured (Table 2) and used in the equation, in lieu of the conventional constant of 3.5 mL·kg−1·min−1. This may have reduced some of the variability in using the American College of Sports Medicine metabolic equation, which also uses assumed constant values for the O2 cost of walking in addition to the V˙O2rest constant. The results suggest that there may be value in measuring V˙O2rest, or at least using reported values of other similar populations rather than relying on the conventional constant value.

The HRR method was similarly accurate across the three groups, suggesting this may be an effective method to use in prescribing exercise intensity for breast cancer patients and survivors. The HRR method is also potentially the most feasible method for clinical use, as it requires only a treadmill or bike and heart rate monitor rather than gas exchange measurement using a metabolic cart in its application. The only variables required to use the HRR method are HRpeak and HRrest. HRpeak is unlikely to be affected by breast cancer treatment (19), but HRrest may change frequently throughout chemotherapy due to side effects and deconditioning and should be measured regularly. Although it has not been investigated, adjusting the target HR with changes in HRrest throughout treatment may be effective in maintaining the accuracy of the HRR method throughout chemotherapy treatment. HRpeak can be estimated from a prediction equation based on age rather than measured in a maximal exercise test, although it is less accurate.

The DIRECT HR method was accurate in the survivor and control groups, consistent with one study that reported high reproducibility in the application technique of this method in a healthy heterogeneous sample (29). However, the DIRECT HR method was significantly less accurate in the patient group, which is the group most likely to exhibit an altered heart rate response to exercise (due to anemia and the cardiotoxic effects of treatment), the condition for which the DIRECT HR method is reported to be particularly useful (27). In addition to low accuracy, this method also showed great variability in achieved intensity in the patient group in particular, ranging from 35% to 77% V˙O2R. Exercise intensities of 60%–84% V˙O2R are reported to be more effective at increasing V˙O2peak than 40%–59% V˙O2R (26). If this method were used in an exercise intervention for the patient group, the widely varied exercise stimulus could affect amount of improvement in aerobic fitness and other outcome measures influenced by exercise training. In addition, the relationship between heart rate and oxygen consumption, on which the DIRECT HR method is based, has previously been reported to change after adjuvant chemotherapy treatment for breast cancer (20), indicating this method would also not be accurate throughout the duration of chemotherapy treatment. Therefore, the DIRECT HR method may not be effective in breast cancer patients during or immediately after adjuvant chemotherapy treatment but remains a reasonable option for intensity prescription in breast cancer survivors and healthy controls.

The accuracy of the RPE method was higher in the patient and control groups than that in the survivor group. RPE is suggested to integrate peripheral signals from working muscles and joints and central signals from cardiovascular and respiratory function (3). There are short-term side effects of chemotherapy, such as muscle and joint pain (23), anemia, subclinical cardiac damage (17), and cognitive alterations, such as memory and information processing speed loss (28), that could affect the interpretation and processing of these signals, potentially leading to differences between the study groups. No difference between breast cancer survivors and healthy controls was reported previously in the estimation of RPE during ongoing exercise (10); however, the current results indicate that the production of an intensity from memory required to use RPE in prescription is different between these groups.

In nearly all participants in the patient and survivor groups, the achieved intensity for the RPE method was lower than prescribed, and the minimum values of achieved intensity for each group were markedly lower than the prescribed intensity (46% and 37% V˙O2R, respectively). As previously mentioned, intensities at and below 59% V˙O2R are less effective at increasing V˙O2peak (26). The main objective during chemotherapy treatment may be maintenance of fitness rather than improvement. During this time, exercise at a lower than intended intensity may be less of a concern than that in the survivor stage, where the priority may shift to rehabilitation, which includes a focus on gaining the optimal health and fitness benefits from exercise. Furthermore, HRR, DIRECT HR, and METW were all more than 50% more accurate than the RPE method in the survivor group, indicating the clear advantage of using objective physiological data in this population. Regardless of group differences, this subjective assessment of exercise intensity was not an accurate means of prescribing exercise intensity. However, the Borg scale may be used as an adjunct to the other prescription methods to monitor exercise intensity. The combination of the METW method with either of the HR methods may also increase the accuracy of exercise intensity prescription.

A significant strength of the study was the design, which was developed to test the prescription methods pragmatically, as they would be used in a research study or clinical setting. The obvious diversion from practical use of these methods is that the participants were required to wear the pneumotach and tubing to collect the expired gas to measure the actual exercise intensity. This experience can cause anxiety, especially in individuals who have never undergone cardiopulmonary exercise testing previously. Walking on a treadmill can also cause anxiety in inexperienced individuals. Anxiety and fear are known to cause rising levels of catecholamines, which is associated with increases in heart rate (4). A related strength of the study is that all subjects in the cancer groups were experienced with both maximal exercise testing with expired gas analysis and treadmill use, thereby reducing the influence of anxiety as a confounding variable. Potential confounding variables such as day-to-day hydration levels, nutrition, and stress were controlled by testing all four exercise intensity prescription methods on the same day, and potential for accumulated fatigue was controlled by randomization of the order of the methods, returning the participants to near-baseline levels before testing the next method.

The study design has some limitations. The percentage of maximal heart rate method is commonly used in all populations to prescribe exercise intensity, including breast cancer research, due to its ease of use. However, this method has several limitations, including the mismatch between exercise intensity (% V˙O2R) and the percentage of maximal heart rate. Because this method is used without regard for a desired V˙O2, it could not be compared in its ability to achieve a desired % V˙O2R and was therefore not compared in this study. The accuracy of the exercise intensity prescription methods used in this study was only tested for one level of exercise intensity, and different results may have occurred for lower or higher intensity levels. The intensity level of 60% V˙O2R was chosen because it is at the borderline of moderate and hard intensity classifications (13), and it is commonly used and recommended in exercise prescriptions for breast cancer survivors (6). More research is needed to confirm the applicability of the findings to other exercise intensities. The results are only applicable to a narrow age range (40–65 yr), which was specifically chosen to be representative of breast cancer survivors (1), while minimizing the confounding effect of aging (24). The cross-sectional study design was convenient for the purpose of comparing the three groups but does not provide any information regarding the accuracy of these methods over time. This limitation is especially applicable to the patient group, as some side effects of chemotherapy treatment, especially cardiotoxicity, may be cumulative and progress in severity with each administration (11). Lastly, a larger sample size in each group may have helped to identify some additional differences between the groups.

The differences in the accuracy of exercise intensity prescription methods between groups reported in this study indirectly suggest possible differences in the physiological response to exercise among those who have recently received chemotherapy and those who have completed initial treatment for breast cancer and healthy controls. Future studies are needed to directly describe and quantify alterations in the response to exercise throughout the continuum of breast cancer, including at the time of diagnosis throughout treatments, and in recovery and rehabilitation after treatment.

In summary, the accuracy of the HRR and the METW methods was not affected by cancer treatment status, and both methods were accurate and achieved the prescribed exercise intensity across all three groups. In settings where ease of use is required, the HRR method is the optimal exercise intensity prescription method for breast cancer patients who have recently finished chemotherapy and survivors who have completed chemotherapy and radiation. The requirement of periodic testing of V˙O2peak throughout treatment or exercise training to maintain accuracy should be considered in using the METW method. The DIRECT HR method was inaccurate and variable in the patient group, and thus may not be an appropriate choice, but was less variable in the survivor group and could be used effectively in this group. The RPE method, which uses a subjective assessment of exercise intensity, was the least accurate method for all groups. Future research is needed to investigate the mechanisms underlying the differences in the accuracy of exercise intensity prescription methods among the breast cancer patients, survivors, and healthy controls.

The project was supported by student grants for the first author from Canadian Institutes of Health Research, the Michael Smith Foundation for Health Research, and the Lotte and John Hecht Memorial Foundation.

The authors do not have any relationships to disclose that would cause a conflict of interest.

The results of the present study do not constitute endorsement by the American College of Sports Medicine.